Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

CSHL team solves a protein complex's molecular structure to explain its role in gene silencing

14.11.2011
A cell's genome maintains its integrity by organizing some of its regions into a super-compressed form of DNA called heterochromatin.

In the comparatively simple organism fission yeast, a cellular phenomenon known as RNA interference (RNAi) plays an essential role in assembling heterochromatin, which keeps the compressed DNA in an inactive or "silent" state. Central to this process is a large protein complex that physically anchors various molecules involved in heterochromatin assembly to the chromatin fibers.

By probing the three dimensional structure of this protein complex, called RNA-Induced Initiation of Transcriptional gene Silencing (RITS), scientists from Cold Spring Harbor Laboratory (CSHL) and their collaborators at St. Jude's Research Hospital have discovered new details of how its various parts or "domains" contribute to heterochromatin assembly and gene silencing. The study appears in Nature Structural & Molecular Biology on Nov. 13.

"Heterochromatin formation relies on the RNAi pathway, and the RITS complex is the central, linking player that makes this possible," explains CSHL Professor and HHMI Investigator Leemor Joshua-Tor, Ph.D. The RITS complex is composed of three proteins, including Ago1, a key component of the cell's RNAi machinery. When Ago1 binds to small interfering RNAs (siRNAs) that originate from a specific genomic region, it helps shut down the activity of that genomic region.

The second member of the RITS complex is a protein called Chp1, which acts like a molecular Velcro that specifically attaches to those areas of chromatin that have been chemically marked by methyl groups. The third RITS component is a largely flexible protein called Tas3 that bridges Chp1 and Ago1.

"Our strategy to understand how these various modules of the RITS complex work has been to find out what these structures look like and how they connect to each other and to chromatin," says Joshua-Tor. For the last few years, her team has explored these questions in fission yeast.

In the current study, the combined use of X-ray crystallography and biochemisty by Research Investigator Thomas Schalch, Ph.D., has yielded a much better picture and revealed further details of how Chp1 interacts with the Tas3 protein. These experiments have also identified a previously unknown substructure at the very end of Chp1.

A clue about what role this structure, called the PIN domain, might play in heterochromatin assembly came from scouring a protein database. The team found that other proteins that had similar structural features were associated with telomeres, the cap-like structures at the end of chromosomes. In fission yeast, telomeres are one of the locations where heterochromatin is found, another being the centromere -- the dense knob-like structure at the center of a chromosome.

The team found that deleting the PIN domain from Chp1 prevented heterochromatin formation at the telomeres but didn't affect formation at the centromere. "This suggests different functions of RITS proteins at centromeres vs telomeres," says Joshua-Tor. "RITS might be exerting its effect at centromeres through Ago1 and the RNAi machinery, but might enforcing its function at the telomeres through Chp1 and its PIN domain." The team is now turning its focus to understanding how these various functions are regulated.

"The Chp1-Tas3 core is a multifunctional platform critical for gene silencing by RITS," appears in Nature Structural & Molecular Biology on Nov. 13. The full citation is Thomas Schalch, Godwin Job, Sreenath Shanker, Janet F Partridge & Leemor Joshua-Tor.

About Cold Spring Harbor Laboratory

Founded in 1890, Cold Spring Harbor Laboratory (CSHL) has shaped contemporary biomedical research and education with programs in cancer, neuroscience, plant biology and quantitative biology. CSHL is ranked number one in the world by Thomson Reuters for impact of its research in molecular biology and genetics. The Laboratory has been home to eight Nobel Prize winners. Today, CSHL's multidisciplinary scientific community is more than 350 scientists strong and its Meetings & Courses program hosts more than 11,000 scientists from around the world each year. Tens of thousands more benefit from the research, reviews, and ideas published in journals and books distributed internationally by CSHL Press. The Laboratory's education arm also includes a graduate school and programs for undergraduates as well as middle and high school students and teachers. CSHL is a private, not-for-profit institution on the north shore of Long Island. For more information, visit http://www.cshl.edu.

Hema Bashyam | EurekAlert!
Further information:
http://www.cshl.edu

More articles from Life Sciences:

nachricht New gene potentially involved in metastasis identified
26.03.2019 | Institute of Science and Technology Austria

nachricht Decoding the genomes of duckweeds: low mutation rates contribute to low genetic diversity
26.03.2019 | Westfälische Wilhelms-Universität Münster

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: New gene potentially involved in metastasis identified

Gene named after Roman goddess Minerva as immune cells get stuck in the fruit fly’s head

Cancers that display a specific combination of sugars, called T-antigen, are more likely to spread through the body and kill a patient. However, what regulates...

Im Focus: The taming of the light screw

DESY and MPSD scientists create high-order harmonics from solids with controlled polarization states, taking advantage of both crystal symmetry and attosecond electronic dynamics. The newly demonstrated technique might find intriguing applications in petahertz electronics and for spectroscopic studies of novel quantum materials.

The nonlinear process of high-order harmonic generation (HHG) in gases is one of the cornerstones of attosecond science (an attosecond is a billionth of a...

Im Focus: Magnetic micro-boats

Nano- and microtechnology are promising candidates not only for medical applications such as drug delivery but also for the creation of little robots or flexible integrated sensors. Scientists from the Max Planck Institute for Polymer Research (MPI-P) have created magnetic microparticles, with a newly developed method, that could pave the way for building micro-motors or guiding drugs in the human body to a target, like a tumor. The preparation of such structures as well as their remote-control can be regulated using magnetic fields and therefore can find application in an array of domains.

The magnetic properties of a material control how this material responds to the presence of a magnetic field. Iron oxide is the main component of rust but also...

Im Focus: Self-healing coating made of corn starch makes small scratches disappear through heat

Due to the special arrangement of its molecules, a new coating made of corn starch is able to repair small scratches by itself through heat: The cross-linking via ring-shaped molecules makes the material mobile, so that it compensates for the scratches and these disappear again.

Superficial micro-scratches on the car body or on other high-gloss surfaces are harmless, but annoying. Especially in the luxury segment such surfaces are...

Im Focus: Stellar cartography

The Potsdam Echelle Polarimetric and Spectroscopic Instrument (PEPSI) at the Large Binocular Telescope (LBT) in Arizona released its first image of the surface magnetic field of another star. In a paper in the European journal Astronomy & Astrophysics, the PEPSI team presents a Zeeman- Doppler-Image of the surface of the magnetically active star II Pegasi.

A special technique allows astronomers to resolve the surfaces of faraway stars. Those are otherwise only seen as point sources, even in the largest telescopes...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

International Modelica Conference with 330 visitors from 21 countries at OTH Regensburg

11.03.2019 | Event News

Selection Completed: 580 Young Scientists from 88 Countries at the Lindau Nobel Laureate Meeting

01.03.2019 | Event News

LightMAT 2019 – 3rd International Conference on Light Materials – Science and Technology

28.02.2019 | Event News

 
Latest News

Searching for disappeared anti-matter: A successful start to measurements with Belle II

26.03.2019 | Physics and Astronomy

Extremely accurate measurements of atom states for quantum computing

26.03.2019 | Physics and Astronomy

Listening to the quantum vacuum

26.03.2019 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>